ChemicalBook CAS DataBase List Hydrocortisone

Hydrocortisone synthesis

10synthesis methods

Product Name:Hydrocortisone
CAS Number:50-23-7
Molecular formula:C21H30O5
Molecular Weight:362.47

Hydrocortisone, 11β,17α,21-trihydroxypregn-4-en-3,20-dione (27.1.8), is synthesized in various ways and from various compounds containing a steroid skeleton. According to one of them, hydrocortisone is synthesized from dextropregnenolone. The double bond between C16 and C17 of dextropregnenolone is oxidized using hydrogen peroxide in a base, forming an epoxide 27.1.1. Interacting this with hydrobromic acid opens the epoxide ring, forming 16-bromo-17-hydroxydextropregnenolone (27.1.2). The resulting bromo derivative undergoes debromination by hydrogen using a palladium on carbon catalyst, and then the secondary hydroxyl group undergoes esterification using formic acid in the presence of p-toluenesulfonic acid, giving 3-formyloxy-17-hydroxydextropregnenolone (27.1.3). The resulting 3-formyloxy- 17-hydroxydextropregnenolone undergoes bromination by bromine, which results in bromination of the C4–C5 double bond and the methyl group of acetyl moiety, which forms a tribromo derivative 27.1.4. Reacting the product with sodium iodide results in dehalogenation of the resulting vicinal dibromide, during which the double bond is simultaneously shifted into the position between carbon atoms C5 and C6 that gives the bromoketone 27.1.5. This is reacted with potassium acetate and then with acetic anhydride in the presence of p-toluenesulfonic acid, forming a diacetate 27.1.6. Taking into account that unlike acetates, formates are easily oxidized and give exactly the same products as do the corresponding alcohols, the resulting diacetate is oxidized in an Oppenauer oxidation reaction, using aluminum isopropoxide and cyclohexanone as a hydrogen acceptor. During this, isomerization of the double bond into the primary position between C4 and C5 simultaneously takes place, forming a stable, conjugated vinylketone, after which the acetyl protection of both hydroxyl groups is hydrolyzed using potassium hydroxide, giving 17-hydroxy-11-deoxycorticosterone (27.1.7). This undergoes microbiological oxidation at position C1, forming the desired hydrocortisone (27.1.8). Side reactions of microbiological oxidation using the very same microorganisms can cause hydroxylation of steroids in different positions, using easily accessible progesterone as an initial substance.

50-03-3 Synthesis

50-03-3
568 suppliers
$32.70/1g

50-23-7
748 suppliers
$24.00/1g

Yield:50-23-7 94.82%

Reaction Conditions:

with sodium methylate in methanol at 20; for 0.5 h;

Steps:

2 Synthesis of 11, 17, 21-trihydroxy-pregn-4-ene-3, 20-dione

Compound 2 was synthesized by dissolving 29 mg (0.071 mmol)of compound (1) in 1.5 mL of methanol followed by addition of0.3 mL of sodium methoxide as a catalyst. The mixture was kept atroom temperature for 30 min. The reaction mixture was neutralizedwith IR 120H resin and filtered. Filtrate was concentratedand compound 2 was purified with column chromatography usingChloroform/methanol as eluent yielding 27.5 mg (94.82%) of compound2 in pure state. m.p: 490e491 K, Molecular formula:C21H30O5, 1H NMR in CDCl3 at 300 MHz: d 7.260(D, s, CDCl3), d 0.962(1H, s, H-18), d 1.054, 1.017 (1H, dd, H-9, J 3.3 Hz), d 1.442 (1H, s,H-19), d 3.061 (1H, broad signal, OH-21), d 4.337(1H, d, J 19.8 Hz,H-21A), d 4.686 (1H, d, J 19.8 Hz, H-21B) d 4.468e4.499 (1H,q,J 3 Hz, H-11), d 5.689 (1H, d, H-4, J 1.2 Hz). FT-IR nmax (in cm1):3381.44, 2950.5, 2924.74, 2859.79, 1711.34, 1658.76, 1462.88,1378.35, 1271.13, 1235.05, 1090.72, 1025.77, 869.07, 763.91, 743.29.ESI-MS: 385, 362, 346, 302.

References:

Sethi, Arun;Singh, Ranvijay Pratap;Prakash, Rohit;Amandeep [Journal of Molecular Structure,2017,vol. 1130,p. 860 - 866]